Insights & Perspectives Evidence for a cell cycle checkpoint that senses branched actin in the

A fascinating paper by James Bearand colleagues has recently raised thepossibility that branched actin net-works, nucleated by the Arp2/3 com-plex, might be sensed by the cell andprovide an essential signal for cell cycleprogression in untransformed cells [1].In this work, the authors knocked downthe expression of the Arp2/3 complex inmouse embryonicfibroblast (MEF) cells.Knocked down cells did not proliferate,unless the tumor suppressor Arf wasgenetically inactivated. This importantobservation suggested that the Arp2/3activitywasnotrequiredperse,becauseit nucleates an essential cytoskeletalstructure. Rather it suggested thatbranchedactinnetworksweresomehowsensed and that downstream an essen-tial ‘‘go’’ signal was delivered to the cellcycle machinery (Fig. 1). The situationappearsanalogoustothewell-established‘‘spindle assembly checkpoint’’ (SAC).SAC makes sure that all chromosomesare well attached to the aster microtu-bules at the metaphase stage of mitosis,before progressing to correct separationof chromosomes into the two daughtercells at the anaphase stage [2]. In cancercells,wheretheSACisnotoperative,cellsdo not stop in response to drugs depoly-merizing microtubules. They also experi-enceprematuremetaphase,whichresultsin defects in chromosome segregationand aneuploidy.Previous evidence suggested thatactin filaments might be sensed likemicrotubules through a checkpoint.Cytochalasin drugs that impair actinpolymerization stop the cell cycle [3–5].This effect could be due to a requirementfor the actin cytoskeleton to progressthroughmitosis,forexampleduring con-striction of the cleavage furrow, which ismediated by myosin motors walking onactin filaments. This cell cycle block,however, was observed even when verylow doses of cytochalasin, which had novisible effects on cleavage or adhesion,were used [5]. The cytochalasin-inducedblockoccurredinG1,andthisG1blockwas alleviated when p53 or Rb tumorsuppressors were inactivated [4, 5](Table 1). Again such a rescue suggestedaspecificsignalingpathwayfromtheactinstructure to cell cycle machineries ratherthan a general requirement for actin.Checkpoints are particular signaling path-ways that inform the cell about specificcues, like correct cytoskeleton dynamics.Inthatsense,thisputativesignalingpath-way that might monitor branched actinwould qualify as a checkpoint.